BACKGROUND:Adult stem cell therapy is one of the research hotspots in the field of peripheral nerve injury repair and regeneration.With excellent properties of mesenchymal stem cells such as high acquisition rate,wide source,and rapid proliferation,mesoderm have been regarded as the ideal source of adult stem cells,while ectoderm-derived adult stem cells,especially neural crest stem cells,have certain neurogenic properties and attract more and more attention from researchers. OBJECTIVE:To mainly review the role and mechanism of multifunctional adult stem cells from ectoderm and mesoderm in peripheral nerve injury repair and regeneration,so as to explore the research progress and application prospect of adult stem cells from different sources and discuss the potential application value of adult stem cell therapy and the problems to be solved in connection with clinical studies. METHODS:The first author searched the relevant articles published from December 2001 to February 2024 in PubMed and SinoMed by computer in February 2024.The Chinese and English search terms were"ectodermal stem cells,mesenchymal stem cells,peripheral nerve injury,repair,regeneration."Finally,69 articles were included and analyzed. RESULTS AND CONCLUSION:(1)Ectodermal adult stem cells have excellent differentiation and regeneration potential,especially epidermal neural crest stems cells,olfactory stem cells,and dental ectomesenchymal stem cells,which have certain neurogenic properties and can express neural specific markers in vitro.However,relevant clinical research needs to be accumulated.(2)There are many types of adult stem cells derived from mesoderm,which are easy to obtain and purify.Among them,the efficacy and safety of bone marrow mesenchymal stem cells and umbilical cord mesenchymal stem cells in the repair of peripheral nerve injury are supported by clinical trials;that is,they can improve sensory and motor nerve conduction and there are no complications and obvious adverse reactions in follow-up.The acquisition of bone marrow mesenchymal stem cells needs invasive surgery and requires the patient to match the donor bone marrow type,which limit the application to some extent.Although umbilical cord mesenchymal stem cells do not require invasive harvesting,their isolation is difficult and phenotypically unstable.(3)Adult stem cells derived from endoderm often fail to grow in vitro,so the possibility of clinical application is low.(4)In conclusion,bone marrow mesenchymal stem cells are still the first choice for adult stem cell therapy in the treatment of peripheral nerve injury,which is suitable for cases without surgical contraindications and meeting the matching requirements,followed by umbilical cord mesenchymal stem cells supplemented by improved isolation methods and advanced phenotypic stability strategies.(5)Dental ectomesenchymal stem cells and adipose-derived mesenchymal stem cells have high application potential and need to be further tested in clinical trials.Other adult stem cells derived from ectodermal and mesodermal layers have significant advantages in animal and cell experimental studies due to their excellent properties.

Pancreatitis is an inflammatory disease influenced by both environmental and genetic factors. It has a high prevalence and mortality rate worldwide, with no radical cure. Breakthroughs have been recently made in genetic research of pancreatitis. Susceptibility genes and pathways have been continuously discovered, which highlighted the roles of genetic factors in hypertriglyceridemic and chronic pancreatitis. Gene therapy may offer radical cure for pancreatitis, though it has remained at the research phase. This article has reviewed the genetic pathogenesis of pancreatitis and current status of gene therapy research, with an aim to provide a reference for attaining definitive cure for the disease.
Humans ; Genetic Therapy/methods* ; Pancreatitis/etiology* ; Genetic Predisposition to Disease ; Animals

Pancreatitis is an inflammatory disease influenced by both environmental and genetic factors. It has a high prevalence and mortality rate worldwide, with no radical cure. Breakthroughs have been recently made in genetic research of pancreatitis. Susceptibility genes and pathways have been continuously discovered, which highlighted the roles of genetic factors in hypertriglyceridemic and chronic pancreatitis. Gene therapy may offer radical cure for pancreatitis, though it has remained at the research phase. This article has reviewed the genetic pathogenesis of pancreatitis and current status of gene therapy research, with an aim to provide a reference for attaining definitive cure for the disease.

Pancreatitis is an inflammatory disease influenced by both environmental and genetic factors. It has a high prevalence and mortality rate worldwide, with no radical cure. Breakthroughs have been recently made in genetic research of pancreatitis. Susceptibility genes and pathways have been continuously discovered, which highlighted the roles of genetic factors in hypertriglyceridemic and chronic pancreatitis. Gene therapy may offer radical cure for pancreatitis, though it has remained at the research phase. This article has reviewed the genetic pathogenesis of pancreatitis and current status of gene therapy research, with an aim to provide a reference for attaining definitive cure for the disease.

Objective:To analyze the mutation spectrum and regional distribution of susceptibility pathogenic genes in Chinese chronic pancreatitis (CP) patients.Methods:A retrospective analysis was conducted on 1 758 sporadic CP patients who underwent gene sequencing for pathogenic mutations of four major susceptibility genes ( SPINK1, PRSS1, CTRC, and CFTR) at the First Affiliated Hospital of Naval Medical University from December 2010 to November 2022. Pathogenic mutations of four major susceptibility genes were detected by using the next-generation sequencing, and both known and novel pathogenic mutations were validated by Sanger sequencing. The ethnic and regional distributions of pathogenic mutations across different ethnic groups were compared. The ArcMap 10.7 software was used to provide the distribution map of common CP pathogenic mutations in China, and regional differences of these mutations were assessed. According to seven major geographical regions in China, we also evaluated the enrichment differences of CP pathogenic mutations in North China region, Northeast China region, East China region, Central China region, South China region, Southwest China region, and Northwest China region. Results:Among 1 758 CP patients, 50.23% (883/1 758) carried pathogenic mutations, and the SPINK1 pathogenic mutations were most predominated (39.31%). Among them, c.194+2T>C mutations accounted for 94.21% of all SPINK1 mutations. 32.59% (573/1 758) of patients carried single heterozygous mutation of one susceptibility gene, and 4.61% carried homozygous mutation of SPINK1 c.194+2T>C. There was no statistically significant difference on the overall pathogenic mutation carrying rate between Han and ethnic minority patients, whereas the mutation carrying rate of SPINK1 c.194+2T>C was significantly higher among Han patients than among ethnic minorities (37.48% vs 20.00%, P<0.05). Among 31 provinces and cities, the mutation carrying rate of CP patients in Tianjin, Guangdong, Yunnan, Hubei and Anhui were all higher than 60.00%. The SPINK1 mutations accounted for the highest proportion of pathogenic mutations across all provinces (33.33% to 61.54%), and SPINK1 c.194+2T>C was the most prevalent mutation. The mutation carrying rate of SPINK1 c.194+2T>C was higher than 40.00% in Jilin, Liaoning, Tianjin, Anhui, Jiangxi, Hubei, Henan, and Guangdong. Distribution analysis of seven geographic regions showed that the overall carrying rate of pathogenic mutations in North China region was significantly lower than that in Central China region (represented by Henan, Hubei, and Hunan; 38.38% vs 58.15%), and the differences were statistically significant ( P<0.05). Additionally, although the carrying rate of SPINK1 c.194+2T>C was highest in Central (41.85%) and Northeast China region (38.78%), no significant differences were found among different regions. Conclusions:Genetic factors was the main etiology of CP in China, with SPINK1 c.194+2T>C mutations being most prevalent. The carrying rates of common susceptibility genes of CP were highest in Central China region as well as SPINK1 c.194+2T>C mutation.

Objective:To analyze the mutation spectrum and regional distribution of susceptibility pathogenic genes in Chinese chronic pancreatitis (CP) patients.Methods:A retrospective analysis was conducted on 1 758 sporadic CP patients who underwent gene sequencing for pathogenic mutations of four major susceptibility genes ( SPINK1, PRSS1, CTRC, and CFTR) at the First Affiliated Hospital of Naval Medical University from December 2010 to November 2022. Pathogenic mutations of four major susceptibility genes were detected by using the next-generation sequencing, and both known and novel pathogenic mutations were validated by Sanger sequencing. The ethnic and regional distributions of pathogenic mutations across different ethnic groups were compared. The ArcMap 10.7 software was used to provide the distribution map of common CP pathogenic mutations in China, and regional differences of these mutations were assessed. According to seven major geographical regions in China, we also evaluated the enrichment differences of CP pathogenic mutations in North China region, Northeast China region, East China region, Central China region, South China region, Southwest China region, and Northwest China region. Results:Among 1 758 CP patients, 50.23% (883/1 758) carried pathogenic mutations, and the SPINK1 pathogenic mutations were most predominated (39.31%). Among them, c.194+2T>C mutations accounted for 94.21% of all SPINK1 mutations. 32.59% (573/1 758) of patients carried single heterozygous mutation of one susceptibility gene, and 4.61% carried homozygous mutation of SPINK1 c.194+2T>C. There was no statistically significant difference on the overall pathogenic mutation carrying rate between Han and ethnic minority patients, whereas the mutation carrying rate of SPINK1 c.194+2T>C was significantly higher among Han patients than among ethnic minorities (37.48% vs 20.00%, P<0.05). Among 31 provinces and cities, the mutation carrying rate of CP patients in Tianjin, Guangdong, Yunnan, Hubei and Anhui were all higher than 60.00%. The SPINK1 mutations accounted for the highest proportion of pathogenic mutations across all provinces (33.33% to 61.54%), and SPINK1 c.194+2T>C was the most prevalent mutation. The mutation carrying rate of SPINK1 c.194+2T>C was higher than 40.00% in Jilin, Liaoning, Tianjin, Anhui, Jiangxi, Hubei, Henan, and Guangdong. Distribution analysis of seven geographic regions showed that the overall carrying rate of pathogenic mutations in North China region was significantly lower than that in Central China region (represented by Henan, Hubei, and Hunan; 38.38% vs 58.15%), and the differences were statistically significant ( P<0.05). Additionally, although the carrying rate of SPINK1 c.194+2T>C was highest in Central (41.85%) and Northeast China region (38.78%), no significant differences were found among different regions. Conclusions:Genetic factors was the main etiology of CP in China, with SPINK1 c.194+2T>C mutations being most prevalent. The carrying rates of common susceptibility genes of CP were highest in Central China region as well as SPINK1 c.194+2T>C mutation.

Objective:To evaluate the safety and effectiveness of The Stork OTC conception aid kit for the treatment of male infertility compared with natural sexual intercourse.Methods:A multi-center, prospective, open, self-controlled, randomly crossed trial was performed in 57 infertility couples who were unable to naturally conceive, and were selected in Shanghai General Hospital, Shanghai Jiao Tong University, Reproductive Medicine Center,Tongji Medical College, Huazhong University of Science and Technology and Anhui Provincial Hospital from July 2017 to September 2018. Patients were required to participate both the conception aid kit and natural sexual intercourse in two consecutive periods of ovulation. A random envelope method was used to determine the application sequences of two methods. Twenty-nine couples were treated with the conception aid kit in the first month of ovulation, and applied the natural sexual intercourse in the second month of ovulation as group A. Twenty-eight couples were applied the natural sexual intercourse in the first month of ovulation, and were treated with the conception aid kit in the second month of ovulation as group B. Test results collected from all couples who used the conception aid kit were categorized as the test group data. Meanwhile, test results out of those couples who completed natural sexual intercourse were collected as control group data. Compared with its self-controlled natural sexual intercourse two months before and after, the effectiveness and safety of the conception aid kit was verified by general vaginal examination, routine leucorrhea examination, motile sperm score from post coital test (PCT), pregnancy rate comparison and other methods.Results:The trial was conducted at three clinical trial centers. A total of 57 infertility couples were enrolled. A total of 54 couples were validated eventually including 26 couples in group A and 28 infertility couples in group B. Effectiveness was evaluated. The PCT results showed that the sperm score of test group was 6.11±3.00, and the score of the sperm score of control group was 1.22±0.79. The motile sperm score of test group was 5 times ( P<0.001) than that in control group. In the follow-up, 7 (13.0%) of the couples successfully achieved pregnancy with the conception aid kit, 6 (85.7%) of them had healthy offspring, 1 (14.3%) had spontaneous abortion. No couples were pregnant after natural sexual intercourse. Safety was evaluated. The general examination of the vagina and the routine tests of the vaginal leukorrhea showed no difference between test group and control group. All 54 effective couples who completed the test can successfully use the conception aid kid to place the seminal vesicles containing semen and remove them with the attached pulling thread on time without obvious discomfort. Conclusion:The Stork OTC conception aid kits can effectively treat infertility, significantly increase the number of forward-moving sperm entering the cervix, and significantly increase the pregnancy rate. It is safe, non-invasive, simple, can be easily operate by patients themselves, and meets the needs of clinical applications.

Objective:To evaluate the safety and effectiveness of The Stork OTC conception aid kit for the treatment of male infertility compared with natural sexual intercourse.Methods:A multi-center, prospective, open, self-controlled, randomly crossed trial was performed in 57 infertility couples who were unable to naturally conceive, and were selected in Shanghai General Hospital, Shanghai Jiao Tong University, Reproductive Medicine Center,Tongji Medical College, Huazhong University of Science and Technology and Anhui Provincial Hospital from July 2017 to September 2018. Patients were required to participate both the conception aid kit and natural sexual intercourse in two consecutive periods of ovulation. A random envelope method was used to determine the application sequences of two methods. Twenty-nine couples were treated with the conception aid kit in the first month of ovulation, and applied the natural sexual intercourse in the second month of ovulation as group A. Twenty-eight couples were applied the natural sexual intercourse in the first month of ovulation, and were treated with the conception aid kit in the second month of ovulation as group B. Test results collected from all couples who used the conception aid kit were categorized as the test group data. Meanwhile, test results out of those couples who completed natural sexual intercourse were collected as control group data. Compared with its self-controlled natural sexual intercourse two months before and after, the effectiveness and safety of the conception aid kit was verified by general vaginal examination, routine leucorrhea examination, motile sperm score from post coital test (PCT), pregnancy rate comparison and other methods.Results:The trial was conducted at three clinical trial centers. A total of 57 infertility couples were enrolled. A total of 54 couples were validated eventually including 26 couples in group A and 28 infertility couples in group B. Effectiveness was evaluated. The PCT results showed that the sperm score of test group was 6.11±3.00, and the score of the sperm score of control group was 1.22±0.79. The motile sperm score of test group was 5 times ( P<0.001) than that in control group. In the follow-up, 7 (13.0%) of the couples successfully achieved pregnancy with the conception aid kit, 6 (85.7%) of them had healthy offspring, 1 (14.3%) had spontaneous abortion. No couples were pregnant after natural sexual intercourse. Safety was evaluated. The general examination of the vagina and the routine tests of the vaginal leukorrhea showed no difference between test group and control group. All 54 effective couples who completed the test can successfully use the conception aid kid to place the seminal vesicles containing semen and remove them with the attached pulling thread on time without obvious discomfort. Conclusion:The Stork OTC conception aid kits can effectively treat infertility, significantly increase the number of forward-moving sperm entering the cervix, and significantly increase the pregnancy rate. It is safe, non-invasive, simple, can be easily operate by patients themselves, and meets the needs of clinical applications.

Objective: To evaluate the outcomes of splenectomy in the treatment of relapsed/refractory autoimmune hemolytic anemia (AIHA). Methods: Retrospective analysis was performed in 30 cases with relapsed/refractory AIHA who were treated with splenectomy in our hospital. The pre- and post-operative blood routine indexes and responses were followed up. Results: Among the 30 relapsed/refractory AIHA patients, 20 were pure AIHA (including 13 patients with warm antibody AIHA, 2 with warm-cold double antibody AIHA and 5 with Coombs negative AIHA) and 10 were Evans syndrome. The short-term response was evaluated 10-14 days after operation, and the overall response rate (ORR) of short-term response was 90% [12 cases in complete response (CR), 6 cases in partial response (PR)] in 20 therapeutic evaluable cases. Among 13 patients with long-term follow-up data, except 3 patients with Evans syndrome died (2 cases were refractory to splenectomy, 1 case relapsed after surgery), the ORR of 10 patients with relapsed/refractory pure AIHA at 6 months and 12 months were 90% (9/10) and 70% (7/10), respectively, with a median follow-up of 14 (4-156) months. At the end of follow-up, 3 cases had maintained CR for more than 3 years. Conclusion The short-term response of splenectomy as a second-line treatment for relapsed/refractory AIHA is satisfactory, and long-term outcome of splenectomy is up to 70% at 1 year. Approximately one-third of patients could maintain sustained remission.

Objective: To compare the effects of different hemolytic diseases on the level of glycosylated hemoglobin (HbA_1c) to further explore the relationship between HbA_1c and laboratory indexes to disclose implications of HbA_1c in hemolytic diseases. Methods: The distribution of 192 decreased HbA_1c cases in 4 categories of hemolytic diseases was analyzed. Laboratory indexes related to hemolysis were tested and analyzed in each kind of disease, and relationship between laboratory indexes and HbA₁c was statistically explored. Results: Diagnoses of decreased HbA_1c cases mainly included erythrocyte membranopathies (88 cases), immunohemolytic anemia (72 cases), hemoglobinopathy (4 cases) and erythrocyte enzymopathy (5 cases). The distribution of HbA₂ and normal HbF subjects in immunohemolytic anemia and hemoglobinopathy was significantly different from those of HbA₂ and / or abnormal HbF subjects (41.7% vs 22.0%, χ²=5.574, P=0.018; 0.7% vs 7.3%, P=0.031). Compared with non-hemolytic disease patients, those who suffered from 4 categories of hemolytic diseases showed lower HbA_1c level and higher reticulocyte percentage (Ret), indirect bilirubin (IBIL) and free hemoglobin (F-Hb). Different levels of Ret, reticulocyte hemoglobin content (Ret-He), mean corpuscular volume (MCV), IBIL and F-Hb among the 4 kinds of diseases were observed, but the causes of the differences were not the same. HbA_1c was negatively correlated with other laboratory indexes in erythrocyte membranopathies and immunohemolytic anemia. Conclusions Hemolytic disease resulted in false lower HbA_1c, but impact of difference on HbA1c between different diseases was not significant. HbA_1c was closely connected to laboratory indexes related to hemolysis, which might have potential implications for hemolytic diseases such as erythrocyte membranopathies and immunohemolytic anemia.